| First Author | Foltz S | Year | 2022 |
| Journal | Am J Physiol Cell Physiol | Volume | 322 |
| Issue | 2 | Pages | C283-C295 |
| PubMed ID | 35020501 | Mgi Jnum | J:322142 |
| Mgi Id | MGI:7256793 | Doi | 10.1152/ajpcell.00350.2021 |
| Citation | Foltz S, et al. (2022) Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5(-/-) mice. Am J Physiol Cell Physiol 322(2):C283-C295 |
| abstractText | Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene (ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of patients with LGMD-R12 are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5(-/-) mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5(-/-) mice were indistinguishable from wild type. Despite these differences, both male and female Ano5(-/-) mice exhibited exercise intolerance. Although exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5(-/-) female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease. |
